Methods of treatment of eosinophilic bronchitis with an anti-IL-5 antibody

ABSTRACT

The present invention relates generally to the methods for the treatment and diagnosis of conditions mediated by IL-5 and excess eosinophil production, and more specifically to mAbs, Fabs, chimeric and humanized antibodies. More particularly, the present invention relates generally to the treatment of eosinophilic bronchitis with an anti-IL-5 antibody or fragment thereof.

This application is a 371 of International Application No.PCT/US2009/038509, filed 27 Mar. 2009, which claims the benefit of U.S.Provisional Application No. 61/040,363, filed 28 Mar. 2008 which areincorporated herein in their entirety.

FIELD OF THE INVENTION

The present invention relates generally to the methods for the treatmentand diagnosis of conditions mediated by IL-5 and excess eosinophilproduction, and more specifically to the treatment of eosinophilicbronchitis with an anti-IL-5 antibody.

BACKGROUND OF THE INVENTION

Eosinophils have been implicated in the pathogenesis of a wide varietyof inflammatory disease states including allergic disorders associatedwith hypersensitivity reactions in the lung tissue (Butterfield et al.,In: Immunopharmacology of Eosinophils, H. Smith and R. Cook, Eds., p.151-192, Academic Press, London (1993)). A notable example is asthma, adisease characterized by reversible obstruction of the airways leadingto non-specific bronchial hyperresponsiveness. This in turn is dependentupon the generation of a chronic inflammatory reaction at the level ofthe bronchial mucosa and a characteristic infiltration by macrophages,lymphocytes and eosinophils. The eosinophil appears to play a centralrole in initiating the mucosal damage typical of the disease (Corriganet al., Immunol. Today, 13:501-507 (1992)). Increased numbers ofactivated eosinophils have been reported in the circulation, bronchialsecretions and lung parenchyma of patients with chronic asthma, and theseverity of the disease, as measured by a variety of lung functiontests, correlates with blood eosinophil numbers (Griffen et al., J.Aller. Clin. Immunol., 67:548-557 (1991)). Increased numbers ofeosinophils, often in the process of degranulation, have also beenrecovered in bronchoalveolar lavage (BAL) fluids of patients undergoinglate asthmatic reactions, and reducing eosinophil numbers, usually as aconsequence of steroid therapy, is associated with improvements inclinical symptoms (Bousquet et al., N. Eng. J. Med., 323:1033-1039(1990)).

Interleukin 5 (IL-5) is a homodimeric glycoprotein producedpredominantly by activated CD4+ T lymphocytes. In man, IL-5 is largelyresponsible for controlling the growth and differentiation ofeosinophils. Elevated levels of IL-5 are detected in the bronchoalveolarlavage washings of asthmatics (Motojima et al., Allergy, 48:98 (1993)).Mice which are transgenic for IL-5 show a marked eosinophilia inperipheral blood and tissues in the absence of antigenic stimulation(Dent et al., J. Exp. Med., 172:1425 (1990)) and anti-murine IL-5monoclonal antibodies have been shown to have an effect in reducingeosinophilia in the blood and tissues of mice (Hitoshi et al., Int.Immunol., 3:135 (1991)) as well as the eosinophilia associated withparasite infection and allergen challenge in experimental animals(Coffman et al., Science, 245:308-310 (1989), Sher et al., Proc. Natl.Acad. Sci., 83:61-65 (1990), Chand et al., Eur. J. Pharmacol.,211:121-123 (1992)).

Eosinophilic airway inflammation, an eosinophilic bronchitis, is thecomponent of asthma known to predict response to treatment withcorticosteroids (Hargreave, F E, J Allergy Clin Immunol, 102:S102-5(1998)). It is identified by sputum eosinophilia and can also occur inpatients without asthma (Hargreave, F E and Paramerwaran, K. Eur RespirJ, 28:264-7 (2006)). In patients with asthma (Jayaram, et al. Eur RespirJ. 27:483-94 (2006)) or chronic obstructive pulmonary disease (Siva, etal. Eur Respir J, 29:906-13 (2007)), normalizing airway eosinophilsimproves asthma control and prevents exacerbation.

Although corticosteroids are extremely effective in suppressingeosinophil numbers and other inflammatory components of asthma andeosinophilic bronchitis, there are concerns about their side effects inboth severe asthmatics and more recently in mild to moderate asthmatics.The only other major anti-inflammatory drug therapies—cromoglycates(cromolyn sodium and nedocromil)—are considerably less effective thancorticosteroids and their precise mechanism of action remains unknown.

At present, there is no outstanding drug which can have aprednisone-sparing effect in the treatment of eosinophilic bronchitis.Thus, there is a need for the methods of the present invention to reduceeosinophils in a human in need thereof.

SUMMARY OF THE INVENTION

In one embodiment of the present invention, methods are provided fortreating eosinophilic bronchitis, comprising administering to said humansuffering from eosinophilic bronchitis a composition comprising at leastone anti-IL-5 antibody.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Study Design as described in Example 1.

FIG. 2: Time until first exacerbation after randomization, as describedin Example 1, section “Primary Outcomes” subsection “Exacerbations”

FIG. 3: Eosinophils in Sputum (Panel A) and Blood (Panel B). Shown arethe mean proportions of eosinophils in sputum and numbers of eosinophilsin blood study entry (V1), 4 weeks after the first infusion of a studydrug (V4), and at the completion of study treatment (V12) in the twostudy groups. In the mepolizumab group, one patient was withdrawnbecause of an adverse event. One patient in the mepolizumab group andnine in the placebo group had an exacerbation before the study wascomplete. V4 sputum was not obtained from one patient. One patient inthe mepolizumab group and one patient in the placebo group were enrolledin the study in error, since they did not have sputum eosinophilia atbaseline. The dashed lines indicate normal values.

DETAILED DESCRIPTION OF THE INVENTION

I. Definitions

As used herein an “anti-IL-5 antibody” refers to any antibody, antibodyfragment or single chain antibody that binds to IL-5 from any species.Antibody fragments include antibodies lacking all or part of animmunoglobulin constant region, e.g., Fv, Fab, or F(ab)₂ and the like.An anti-IL-5 antibody may be murine, chimeric, humanized or fully human.The antibody may be neutralizing. Several examples of anti-IL-5antibodies are described in U.S. Pat. Nos. 5,683,892, 5,693,323,5,783,184, 5,851,525, 6,129,913, 5,096,071, 6,056,957, and 6,451,982herein incorporated by reference in their entirety. In addition,humanized anti-IL-5 antibodies are described in various references andinclude relizumab (SCH55700) and mepolizumab (SB240563) (Greenfeder, etal., Respiratory Research, 2(2):71-79 (2001)). Mepolizumab (SB-240563)is a fully humanized monoclonal antibody (IgG₁, kappa, mAb) which isspecific for human interleukin-5 (IL-5). Other anti-IL-5 antibodies aredescribed in U.S. Pat. Nos. 7,422,742 and 7,141,653 also incorporatedherein by reference.

“Neutralizing” refers to an antibody that inhibits IL-5 activity bypreventing the binding of human IL-5 to its specific receptor or byinhibiting the signalling of IL-5 through its receptor, should bindingoccur. A mAb is neutralizing if it is 90% effective, 95% effective or100% effective in inhibiting IL-5 activity as measured in the B13 cellbioassay. Antibody binding can be measured by a number of assays knownin the art including using a BIAcore optical biosensor (PharmaciaBiosensor, Uppsala, Sweden) and/or an ELISA assay.

The term “high affinity” refers to an antibody having a binding affinitycharacterized by a K_(d) equal to or less than 3.5×10⁻¹¹ M for humanIL-5 as determined by optical biosensor anaylsis. The K_(d) for IL-5 ofa Fab fragment might be estimated to be about 9×10⁻¹¹ M as determined byoptical biosensor.

By “binding specificity for human IL-5” is meant that the antibody has ahigher affinity for human IL-5 compared with any non-human IL-5orthologue such as, but not limited to, murine IL-5. For instance, anantibody with binding specificity for human IL-5 might have a K_(d)equal to or less than 2.2×10⁻¹¹M for human IL-5 while having a K_(d) ofgreater than 2.2×10⁻¹¹M for non-human IL-5 orthologue.

The terms Fv, Fc, Fd, Fab, or F(ab)₂ are used with their standardmeanings (see, e.g., Harlow et al., Antibodies A Laboratory Manual, ColdSpring Harbor Laboratory, (1988)).

As used herein, an “engineered antibody” describes a type of alteredantibody, i.e., a full-length synthetic antibody (e.g., a chimeric orhumanized antibody as opposed to an antibody fragment) in which aportion of the light and/or heavy chain variable domains of a selectedacceptor antibody are replaced by analogous parts from one or more donorantibodies which have specificity for the selected epitope. For example,such molecules may include antibodies characterized by a humanized heavychain associated with an unmodified light chain (or chimeric lightchain), or vice versa. Engineered antibodies may also be characterizedby alteration of the nucleic acid sequences encoding the acceptorantibody light and/or heavy variable domain framework regions in orderto retain donor antibody binding specificity. These antibodies cancomprise replacement of one or more CDRs (preferably all) from theacceptor antibody with CDRs from a donor antibody described herein.

A “chimeric antibody” refers to a type of engineered antibody whichcontains naturally-occurring variable region (light chain and heavychains) derived from a donor antibody in association with light andheavy chain constant regions derived from an acceptor antibody.

A “humanized antibody” refers to a type of engineered antibody havingits CDRs derived from a non-human donor immunoglobulin, the remainingimmunoglobulin-derived parts of the molecule being derived from one (ormore) human immunoglobulin(s). In addition, framework support residuesmay be altered to preserve binding affinity (see, e.g., Queen et al.,Proc. Natl. Acad Sci USA, 86:10029-10032 (1989), Hodgson et al.,Bio/Technology, 9:421 (1991)).

The term “donor antibody” refers to an antibody (monoclonal orrecombinant) which contributes the nucleic acid sequences of itsvariable regions, CDRs, or other functional fragments or analogs thereofto a first immunoglobulin partner, so as to provide the alteredimmunoglobulin coding region and resulting expressed altered antibodywith the antigenic specificity and neutralizing activity characteristicof the donor antibody. One donor antibody suitable for use in thisinvention is a non-human neutralizing monoclonal antibody (i.e., murine)designated as 2B6 (see U.S. Pat. Nos. 5,683,892, 5,693,323, 5,783,184,5,851,525, and 6,129,913 herein incorporated by reference in theirentirety). The antibody 2B6 is defined as a high affinity, human-IL-5specific (i.e., does not recognize murine IL-5), neutralizing antibodyof isotype IgG₁ having the variable light chain DNA and amino acidsequences of SEQ ID NOs: 2 and 16, respectively, and the variable heavychain DNA and amino acid sequences of SEQ ID NOs: 1 and 15,respectively, on a suitable murine IgG constant region.

The term “acceptor antibody” refers to an antibody (monoclonal orrecombinant) heterologous to the donor antibody, which contributes all(or any portion, but preferably all) of the nucleic acid sequencesencoding its heavy and/or light chain framework regions and/or its heavyand/or light chain constant regions to the first immunoglobulin partner.Preferably a human antibody is the acceptor antibody.

“CDRs” are defined as the complementarity determining region amino acidsequences of an antibody which are the hypervariable regions ofimmunoglobulin heavy and light chains. See, e.g., Kabat et al.,Sequences of Proteins of Immunological Interest, 4th Ed., U.S.Department of Health and Human Services, National Institutes of Health(1987). There are three heavy chain and three light chain CDRs (or CDRregions) in the variable portion of an immunoglobulin. Thus, “CDRs” asused herein refers to all three heavy chain CDRs, or all three lightchain CDRs (or both all heavy and all light chain CDRs, if appropriate).

CDRs provide the majority of contact residues for the binding of theantibody to the antigen or epitope. CDRs of interest in this inventionare derived from donor antibody variable heavy and light chainsequences, and include analogs of the naturally occurring CDRs, whichanalogs also share or retain the same antigen binding specificity and/orneutralizing ability as the donor antibody from which they were derived.

By ‘sharing the antigen binding specificity or neutralizing ability’ ismeant, for example, that although mAb 2B6 (see U.S. Pat. Nos. 5,683,892,5,693,323, 5,783,184, 5,851,525, and 6,129,913 herein incorporated yreference) may be characterized by a certain level of antigen affinity,a CDR encoded by a nucleic acid sequence of 2B6 in an appropriatestructural environment may have a lower, or higher affinity. It isexpected that CDRs of 2B6 in such environments will neverthelessrecognize the same epitope(s) as 2B6. Exemplary heavy chain CDRs of 2B6include SEQ ID NO: 7; SEQ ID NO: 8; SEQ ID NO: 9; and exemplary lightchain CDRs of 2B6 include SEQ ID NO: 10; SEQ ID NO: 11; and SEQ ID NO:12.

A “functional fragment” is a partial heavy or light chain variablesequence (e.g., minor deletions at the amino or carboxy terminus of theimmunoglobulin variable region) which retains the same antigen bindingspecificity and/or neutralizing ability as the antibody from which thefragment was derived.

An “analog” is an amino acid sequence modified by at least one aminoacid, wherein said modification can be chemical or a substitution or arearrangement of a few amino acids (i.e., no more than 10), whichmodification permits the amino acid sequence to retain the biologicalcharacteristics, e.g., antigen specificity and high affinity, of theunmodified sequence. For example, (silent) mutations can be constructed,via substitutions, when certain endonuclease restriction sites arecreated within or surrounding CDR-encoding regions.

Analogs may also arise as allelic variations. An “allelic variation ormodification” is an alteration in the nucleic acid sequence encoding theamino acid or peptide sequences of the invention. Such variations ormodifications may be due to degeneracy in the genetic code or may bedeliberately engineered to provide desired characteristics. Thesevariations or modifications may or may not result in alterations in anyencoded amino acid sequence.

The term “effector agents” refers to non-protein carrier molecules towhich the altered antibodies, and/or natural or synthetic light or heavychains of the donor antibody or other fragments of the donor antibodymay be associated by conventional means. Such non-protein carriers caninclude conventional carriers used in the diagnostic field, e.g.,polystyrene or other plastic beads, polysaccharides, e.g., as used inthe BIAcore [Pharmacia] system, or other non-protein substances usefulin the medical field and safe for administration to humans and animals.Other effector agents may include a macrocycle, for chelating a heavymetal atom, or radioisotopes. Such effector agents may also be useful toincrease the half-life of the altered antibodies, e.g., polyethyleneglycol.

“Polypeptide” refers to any peptide or protein comprising two or moreamino acids joined to each other by peptide bonds or modified peptidebonds, i.e., peptide isosteres. “Polypeptide” refers to both shortchains, commonly referred to as peptides, oligopeptides or oligomers,and to longer chains, generally referred to as proteins. Polypeptidesmay contain amino acids other than the 20 gene-encoded amino acids.“Polypeptides” include amino acid sequences modified either by naturalprocesses, such as posttranslational processing, or by chemicalmodification techniques that are well known in the art. Suchmodifications are well described in basic texts and in more detailedmonographs, as well as in a voluminous research literature.Modifications can occur anywhere in a polypeptide, including the peptidebackbone, the amino acid side-chains and the amino or carboxyl termini.It will be appreciated that the same type of modification may be presentin the same or varying degrees at several sites in a given polypeptide.Also, a given polypeptide may contain many types of modifications.Polypeptides may be branched as a result of ubiquitination, and they maybe cyclic, with or without branching. Cyclic, branched and branchedcyclic polypeptides may result from posttranslation natural processes ormay be made by synthetic methods. Modifications include acetylation,acylation, ADP-ribosylation, amidation, covalent attachment of flavin,covalent attachment of a heme moiety, covalent attachment of anucleotide or nucleotide derivative, covalent attachment of a lipid orlipid derivative, covalent attachment of phosphotidylinositol,cross-linking, cyclization, disulfide bond formation, demethylation,formation of covalent cross-links, formation of cysteine, formation ofpyroglutamate, formylation, gamma-carboxylation, glycosylation, GPIanchor formation, hydroxylation, iodination, methylation,myristoylation, oxidation, proteolytic processing, phosphorylation,prenylation, racemization, selenoylation, sulfation, transfer-RNAmediated addition of amino acids to proteins such as arginylation, andubiquitination. See, for instance, PROTEINS—STRUCTURE AND MOLECULARPROPERTIES, 2nd Ed., T. E. Creighton, W. H. Freeman and Company, NewYork, 1993 and Wold, F., Posttranslational Protein Modifications:Perspectives and Prospects, pgs. 1-12 in POSTTRANSLATIONAL COVALENTMODIFICATION OF PROTEINS, B. C. Johnson, Ed., Academic Press, New York,1983; Seifter, et al., “Analysis for protein modifications andnonprotein cofactors”, Meth. Enzymol. (1990) 182:626-646 and Rattan, etal., “Protein Synthesis: Posttranslational Modifications and Aging”, AnnNY Acad Sci (1992) 663:48-62.

“Variant” as the term is used herein, is a polynucleotide or polypeptidethat differs from a reference polynucleotide or polypeptiderespectively, but retains essential properties. A typical variant of apolynucleotide differs in nucleotide sequence from another, referencepolynucleotide. Changes in the nucleotide sequence of the variant may ormay not alter the amino acid sequence of a polypeptide encoded by thereference polynucleotide. Nucleotide changes may result in amino acidsubstitutions, additions, deletions, fusions and truncations in thepolypeptide encoded by the reference sequence, as discussed below. Atypical variant of a polypeptide differs in amino acid sequence fromanother, reference polypeptide. Generally, differences are limited sothat the sequences of the reference polypeptide and the variant areclosely similar overall and, in many regions, identical. A variant andreference polypeptide may differ in amino acid sequence by one or moresubstitutions, additions, deletions in any combination. A substituted orinserted amino acid residue may or may not be one encoded by the geneticcode. A variant of a polynucleotide or polypeptide may be a naturallyoccurring such as an allelic variant, or it may be a variant that is notknown to occur naturally. Non-naturally occurring variants ofpolynucleotides and polypeptides may be made by mutagenesis techniquesor by direct synthesis.

As used herein “eosinophilic bronchitis” refers to a condition in whicha mammal has quantitative sputum cell counts (eosinophils greater than2%) which is responsive to corticosteroid treatment. It may occur aloneor in association with asthma or in some patients with chronicobstructive pulmonary disease (COPD). Typically, in comparison toasthmatic patients, those with eosinophilic bronchitis experience thesymptom of cough alone and have both normal lung function and airwayresponsiveness (Thomson and Chaudhuri American Journal of Respiratoryand Critical Care Medicine 170:4-5 (2004), and Gibson, et al. Thorax57:178-182 (2002)). In most patients the eosinophilic bronchitisresponds to treatment with inhaled steroids but in some it requires aminimum dose of prednisone to keep it controlled. Eosinophilicbronchitis and/or asthma can be considered severe in a patient when thepatient requires at least 35-40 mg/day of predisone to control thesymptoms of either condition.

As used herein “airway eosinophilia” refers to any disease or disorderin which a patient has any amount of eosinophils in any airway,including but not limited to, lung. Eosinophils may be detected, forexample, in or by biopsy, sputum, and/or lavage. Diseases associatedwith airway eosinophilia include, but are not limited to, eosinophilicasthma, eosinophilic COPD, eosinophilic bronchitis, and airwayeosinophilia associated with viral infections, including, but notlimited to, rhino virus. (Shinohara, et al. Allergol Int. 2008 Dec. 1;57(4); Wos, et al. Am J Respir Crit. Care Med. 2008; Handzel, et al. Tcells. J Immunol. 1998 Feb. 1; 160(3):1279-84. PMID; Mercer, et al.Respir Res. 2005; 6:151; and Saetta, et al. Clin Exp Allerg 1996;26:766-774).

As used herein “refractory asthma” refers to a condition wherein apatient has one or both major criteria and two minor criteria as setforth below:

Table 1: Major criteria and minor criteria for refractory asthma

Major Characteristics In order to achieve control to a level ofmild-moderate persistent asthma: 1. Treatment with continuous or nearcontinuous (≧50% of year) oral corticosteroids 2. Requirement fortreatment with high-dose inhaled corticosteroids: Drug Dose (μg/d) Dose(puffs/d) a. Beclomethasone >1,260 >40 puffs (42 μg/inhalationdipropionate >20 puffs (84 μg/inhalation b. Budesonide >1,200  >6 puffsc. Flunisolide >2,000  >8 puffs d. Fluticasone propionate >880  >8 puffs(110 μg), >4 puffs (220 μg) e. Triamcinolone acetonide >2,000 >20 puffsMinor Characteristics 1. Requirement for daily treatment with acontroller medication in addition to inhaled corticosteroids, e.g.,long-acting β-agonist, theophylline, or leukotriene antagonist 2. Asthmasymptoms requiring short-acting β-agonist use on a daily or near dailybasis 3. Persistent airway obstruction (FEV₁ <80% predicted; diurnal PEFvariability >20%) 4. One or more urgent care visits for asthma per year5. Three or more oral steroid “bursts” per year 6. Prompt deteriorationwith ≦25% reduction in oral or inhaled corticosteroid dose 7. Near fatalasthma event in the past *Requires that other conditions have beenexcluded, exacerbating factors treated, and patient felt to be generallyadherent. Fahy, J. Am. J. Respir. Crit. Care Med., Volume 162, Number 6,December 2000, 2341-2351

As used herein “severe asthma” is meant to include patients withrefractory asthma. Patients with severe asthma may not necessarily haveairflow obstruction all of the time, and may or may not have airwayhyperresponsiveness but may suddenly deteriorate on a background ofrelatively stable disease (on treatment). “Severe asthma” is alsounderstood in the art to be defined by various clinical scales otherthan the ATS such as guidelines set for by Global Strategy for AsthmaManagement and Prevention, Global Initiative for Asthma (GINA) 2007 aswell as other guidelines known in the art.

As used herein, “reduce” or “reducing” eosinophils refers to a decreasein the amount of eosinophils observed in the blood and/or sputum of apatient after administration at least one anti-IL-5 antibody.

As used herein “co-administration” or “co-administering” as used hereinrefers to administration of two or more compounds to the same patient.Co-administration of such compounds may be simultaneous or at about thesame time (e.g., within the same hour) or it may be within several hoursor days of one another. For example, a first compound may beadministered once weekly while a second compound is co-administereddaily.

As used herein “disorder associated with excess eosinophil production”means any disorder or disease in which atypical symptoms may manifestdue to the production of eosinophils. Disorders associated with excesseosinophil production include but are not limited to, eosinophilicbronchitis, atopic asthma, atopic dermatitis, allergic rhinitis,non-allergic rhinitis, asthma, severe asthma, chronic eosinophilicpneumonia, allergic bronchopulmonary aspergillosis, coeliac disease,Churg-Strauss syndrome (periarteritis nodosa plus atopy), eosinophilicmyalgia syndrome, hypereosinophilic syndrome, oedematous reactionsincluding episodic angiodema, helminth infections, eosinophiliaassociated with parasite infection and/or the treatment of parasiticinfection, onchocercal dermatitis and Eosinophil-AssociatedGastrointestinal Disorders, including but not limited to, eosinophilicoesophagitis, eosinophilic gastritis, eosinophilic gastroenteritis,eosinophilic enteritis and eosinophilic colitis, nasal micropolyposisand polyposis, aspirin intolerance, asthma and obstructive sleep apnoea.Eosinophil-derived secretory products have also been associated with thepromotion of angiogenesis and connective tissue formation in tumours andthe fibrotic responses seen in conditions such as chronic asthma,Crohn's disease, scleroderma and endomyocardial fibrosis (Munitz A,Levi-Schaffer F. Allergy 2004; 59: 268-75, Adamko et al. Allergy 2005;60: 13-22, Oldhoff, et al. Allergy 2005; 60: 693-6).

The therapeutic response induced by the methods of this invention isproduced by the binding on an anti-IL-5 antibody to human IL-5 and thussubsequently blocking eosinophil stimulation. Thus, the methods of thepresent invention are highly desirable for those persons experiencingeosinophilic bronchitis.

Methods are provided herein for treating eosinophilic bronchitis,comprising administering to said human suffering from eosinophilicbronchitis a composition comprising at least one anti-IL-5 antibody. Insome aspects, said human suffering from eosinophilic bronchitis hassteroid-dependent eosinophilic bronchitis. In some aspects, the steroidis prednisone and/or prednisolone. The anti-IL antibody may beneutralizing. In another aspect, the at least one anti-IL-5 antibody ishumanized. The least one anti-IL-5 antibody may comprise a heavy chaincomprising SEQ ID NO: 19. The at least one anti-IL-5 antibody maycomprise a light chain comprising SEQ ID NO: 21. In yet another aspect,the human is suffering from at least one additional disorder associatedwith excess eosinophil production selected from the group consisting ofatopic asthma, atopic dermatitis, allergic rhinitis, non-allergicrhinitis, asthma, severe asthma, chronic eosinophilic pneumonia,allergic bronchopulmonary aspergillosis, coeliac disease, Churg-Strausssyndrome, eosinophilic myalgia syndrome, hypereosinophilic syndrome,oedematous reactions including episodic angiodema, helminth infections,eosinophilia associated with parasitic infection and/or the treatment ofparasitic infection, onchocercal dermatitis eosinophilic oesophagitis,eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilicenteritis, eosinophilic colitis, nasal micropolyposis, nasal polyposis,aspirin intolerance asthma, obstructive sleep apnoea, chronic asthma,Crohn's disease, scleroderma and endomyocardial fibrosis.

In yet another aspect, the composition comprising at least one anti-IL-5antibody is administered intravenously. The composition comprising atleast one anti-IL-5 antibody may be administered at a dose of 750 mg.The intravenous dose may be administered intravenously over 30 minutes.In another aspect, the composition comprising at least one anti-IL-5antibody may be administered intravenously over a time range of about 10minutes to about 4 hours or more specifically over a range of about 20minutes to about 60 minutes. In another aspect of the present inventionthe composition comprising at least one anti-IL-5 antibody isadministered subcutaneously, which may be at a dose of 250 mg. Asubcutaneous dose may be administered one to three times or more to ahuman.

In yet another aspect, the human is receiving prednisone and/orprednisolone for said steroid-dependent eosinophilic bronchitis and saidprednisone is reduced by at least about 90% in said human suffering fromsteroid-dependent eosinophilic bronchitis after treatment with saidcomposition comprising at least one anti-IL-5 antibody. The humansuffering from steroid-dependent eosinophilic bronchitis experiences astatistically significant reduction in exacerbations of eosinophilicbronchitis after receiving at least said composition comprising at leastone anti-IL-5 antibody. The eosinophil level in said human are reducedto within normal limits, which is understood in the art and can bemeasured by a variety of methods including, but not limited to,bronchial scrubbing. By way of example, within normal limits wouldinclude, but would not be limited to, quantitative sputum cell countshaving eosinophils less than 2%. The eosinophil levels remain withinnormal limits for at least 8weeks after the last dose of saidcomposition comprising anti-IL-5 antibody. Eosinophil levels may bereduced in blood and/or sputum.

In another aspect, methods are provided for treating a human witheosinophilic bronchitis wherein said composition comprising at least oneanti-IL-5 antibody comprises a first anti-IL-5 antibody and a secondanti-IL-5 antibody. The composition comprising at least one anti-IL-5antibody may be co-administered with a steroid.

The present invention also provides methods for reducing eosinophils ina human in suffering from eosinophilic bronchitis, comprisingadministering a composition comprising a first anti-IL-5 antibody and asecond anti-IL-5 antibody. Methods are also provided herein wherein atleast one anti-IL-5 antibody is co-administered with a steroid.

The current invention also provides use of at least one anti-IL-5antibody in the manufacture of a medicament for the treatment ofeosinophilic bronchitis. The present invention provides use of an antiIL-5 antibody or fragment thereof for treatment of eosinophilicbronchitis comprising administering to a patient in need thereof acomposition comprising at least one anti-IL-5 antibody. Also providedherein are pharmaceutical compositions capable of treating eosinophilicbronchitis or alleviating the symptoms produced thereby and formulatedfor the methods and uses described herein. The present inventionprovides an anti-IL-5 antibody for use in the treatment of eosinophilicbronchitis, for administration alone or in combination with a steroid.The anti-IL-5 antibodies of the present invention also provideanti-IL-antibodies for all of the methods and uses described herein.

EXAMPLES

The following examples illustrate various aspects of this invention. Theresults of Example 1 are published in Parameswaran, et al. The New EnglJ Med 360(10):985-993 (2009), which is incorporated by reference hereinin its entirety.

Example 1

The study was a randomized, placebo-controlled, parallel group trial ofup to 26 weeks. Patients were seen every two weeks and were randomizedto treatment at week 2. Humanized monoclonal antibody to IL-5,mepolizumab, was given at a dose of 750 mg or placebo over 30 minutes atweeks 2, 6, 10, 14, and 18. The dose of prednisone was reduced at weeks6, 10, 14, 18, and 22, except in patients who had required prednisone ina daily dose of 10 mg or more. The variables measured every two weekswere: Juniper Asthma Control Questionnaire (ACQ), symptom Likert score,maximal expiratory flow-volume curves to measure FEV_(s), and slow vitalcapacity (VC) before and 15 minutes after salbutamol 200 μg, sputumquantitative cell counts and blood eosinophils. As a result ofprednisone reduction, the patients could have a clinical exacerbation ordevelop bothersome steroid withdrawal symptoms. Exacerbations weredefined by an increase in salbutamol use of 4 or more puffs/day or ofnocturnal or waking respiratory symptoms on two consecutive days, or bya fall in post-salbutamol FEV_(s)>15% from the randomization visit or bya 2-point change in the Likert score for cough or as decided by theinvestigator.

Spirometry was performed according to the American Thoracic Societyrecommendations (American Thoracic Society, Standardization ofSpirometry, 1994 update, Am J Respir Crit. Care Med, 152:1107-1136(1995)) and predicted values were obtained from Crapo, et al. (Crapo, etal. Am Rev Respir Dis, 123:659-94 (1981)). Asthma control was assessedusing the validated Asthma Control Questionnaire (Juniper, et al, EurRespir J, 14:902-7 (1999)). In addition, symptoms of cough, wheeze,chest tightness and shortness of breath were evaluated for the sevendays prior to each visit on a 7-point Likert scale (7 no symptoms, 1worse) (Guyatt, et al., J Chronic Dis, 40:1129-33 (1987)). Sputum wasinduced and processed as described by Pizzichini, et al. (Pizzichini, etal. Eur Respir J, 9:1174-1180 (1996)). Airway responsiveness tomethacholine was measured using the tidal breathing method described byCockcroft, et al. (Cockcroft, et al. Clin Allergy, 7:235-43 (1977) afterwithholding β-agonists for 24 hours.

Exacerbations for this example were defined as either apatient-initiated increase in their daily dose of albuterol of four ormore puffs to control symptoms of chest tightness or as any one of thefollowing: nocturnal or waking respiratory symptoms on two consecutivedays, a decrease of more than 15% in the FEV₁ from the label atrandomization after the use of albuterol, or a 2-point worsening in theLikert score for cough by the investigators at their discretion on thebasis of general clinical worsening, For the latter exacerbation,sputum-cell counts were not known to the treating physician at the timethis decision was made and were not considered in the definition ofexacerbations.

Exacerbations, unless accompanied by sputum neutrophilia, were treatedwith 30 mg of prednisone for 7 days. During this time, the patient waswithdrawn from the study and was seen again at 2 and 4 weeks. If theexacerbation was accompanied by neutrophilic airway inflammation (totalcell count, >15×10⁶ per gram of sputum; neutrophils, >80%), it wastreated with 500 mg of amoxicillin-clavulanic acid twice daily for 10days; patients with neutrophilic exacerbations were not withdrawn fromthe study, and they continued with the protocol for prednisonereduction.

The sample size was based on the primary outcome of the proportion ofpatients who would have exacerbations in each treatment arm. It wasexpected that all patients on the placebo would exacerbate when the dosewas reduce by 50%, while not more that 4 patients on the active armwould exacerbate for a similar dose reduction. The study had 90% powerto detect this difference. Between group comparisons of normallydistributed data were compared using unpaired-t test and non-normal datawere compared using Median test in an intention-to treat analysis.Proportional data was analyzed using Fisher's exact test. Cumulativeprobability and time to exacerbation between treatment groups werecompared by Cox's proportional hazards methods. All tests were 2-sidedand significance was accepted at 95% level and the analyses were doneusing the Statistical Package for Social Sciences, version 13.0 (SPSS,Chicago, Ill.).

Patients meeting the following inclusion criteria were enrolled in astudy of anti-IL5 monoclonal antibody therapy for eosinophilicbronchitis sputum eosinophilia in patients with asthma chronicallytreated with systemic and high dose inhaled corticosteroids:

-   -   Adult patients, aged 18-70 years, who have been followed as an        outpatient and who have been found to require a minimum dose of        prednisone treatment (in addition to high-dose inhaled steroid        treatment) to prevent frequent exacerbations associated with        induced sputum eosinophilia.    -   Patients who, at screening and baseline visits, demonstrate        sputum eosinophilia and symptoms. The symptoms may effect        activity and sleep but should not, in the opinion of the        treating physician, be severe enough to be of concern.    -   While FEV₁ after withholding bronchodilators appropriately,        before and after inhaled salbutamol (200 mg), and methacholine        PC20 will be measured, these need not be abnormal since the        prednisone is required for the control of eosinophilic        bronchitis and any clinical consequences of this, and because        the bronchitis can occur without these features of asthma.    -   On the same doses of corticosteroids for a least one-month.        The study was divided into 3 sequential study periods as follows        and presented in FIG. 1:

-   Period 1: Symptomatic eosinophilic bronchitis (with or without    asthma) on the same dose of prednisone for 6-weeks or more.

-   Period 2: Standardized prednisone reduction (and inhaled steroid if    prednisone is discontinued during the study treatment) at intervals    of 4-weeks until there is a clinical and eosinophilic exacerbation    or bothersome steroid withdrawal effects.

-   Period 3: Washout.

The patients were seen every 2 weeks. Intravenous injections of ananti-IL-5antibody (mepolizumab) 750 mg or placebo were given at weeks 2,6, 10, 14 and 18. Doses of prednisone were reduced in a standard way. Asummary of patient demographics and baseline characteristics ispresented in Table 2.

TABLE 1 Demographic and Clinical Characteristics of Patients atBaseline* Mepolizumab Characteristics (n = 9) Placebo (n = 11) Age(years) 56.4 ± 10.9 58.2 ± 7.1  Gender, Male (no. of patients) 4 8Height, cm 166.2 ± 14.5  168.6 ± 9.9  Weight, kg 85.8 ± 16.7 89.5 ± 14.9Duration of symptoms, y 13.3 ± 10.3 12.5 ± 9.59 FEV₁ Previous minimum†Value (liters) 1.4 ± 0.6  1.6 ± 0.5 % of predicted value 48 ± 17 52 ± 13Previous maximum† Improvement with bronchodilator (%)  28.4 ± 12.03 24.6± 10.6 Decrease during exacerbation (%) 42.0 ± 16.9 45.5 ± 13.7 Currentpostbronchodilation % of predicted value 66.6 ± 18.3 74.3 ± 17.9 Ratioof FEV₁ to vital capacity (%) 63.8 ± 16.2 65.9 ± 13.1 Sputum eosinophilsMedian 16.6 4.0 Range 1.6-54.3   0-35.3 Duration of daily use ofprednisone (years) 9.3 ± 7.6 8.9 ± 8.5 Prednisone (mg/day) Median 10 10Range 5-25 2.5-20  Inhaled Corticosteroids (μg/day) Median 1000 1000Range 600-2000 1000-2000 Short-acting β-agonist (no. of puffs/week) 10 ±6  9 ± 8 Long-acting β-agonist (no. of patients) 9 9Leukotriene-receptor antagonists (no. of patients) 2 1 Atopy (no. ofpatients) 3 4 Nasal polyp (no. of patients) 3 5 Smoking history of >10pack years (no. of patients) 2 3 *Plus-minus values are means ± SD.Values are those recorded at the time of screening unless otherwisestated. There were no significant differences between the two groups forany of the variables except the number of sputum eosinophils (P = 0.03).FEV₁ denotes forced expiry volume in 1 second. †Previous lowest andhighest values for FEV₁ refer to the historic lowest and highest valuesrecorded since the patients were first seen in the clinic. ‡The dose ofinhaled corticosteroid is the equivalent of inhaled fluticasone.Results

Nineteen of the 20 patients completed the study. One subject whoreceived the active drug was withdrawn from the study after the 3^(rd)infusion because of heart failure, but was included in the analysis.Thus, the main analyses included 20 patients, and the per-protocolanalysis included only the 18 subjects who had airway eosinophilia atbaseline.

Primary Outcomes

Exacerbations

There were 12 asthma exacerbations in the placebo group. Nine wereassociated with sputum eosinophilia and three were associated withsputum neutrophilia, of which two were in a patient who was eventuallytreated for an exacerbation associated with sputum eosinophilia. Thus,10 of the 11 patients in the placebo group had exacerbations that led totreatment with prednisone or antibiotics. In contrast, there were twoevents in the mepolizumab arm (1 neutrophilic exacerbation and onewithdrawal due to adverse event) (p=0.008). Exacerbations wereidentified by a decline in FEV_(s) and additional criteria in sevenpatients (one in the active treatment group and six in the placebogroup), by an increase in β₂-agonist rescue (three patients in theplacebo group), and by nocturnal symptoms (one patient in the placebogroup). A change in the Likert scale alone or physician discretion wasnot used in any patient to identify an exacerbation or initiate a changein prednisone dose. The median time to exacerbation (irrespective oftype of bronchitis) was 12 weeks in the placebo group and 20 weeks inthe mepolizumab group (p=0.003). (FIG. 2).

There were also no exacerbations associated with neutrophilic bronchitisin the mepolizumab group while there were 3 in the placebo group.

Reduction in Prednisone Dose

In the mepolizumab group, patients had a mean (±SD) reduction ofprednisone by 83.8%±33.4% of the maximum possible reduction per protocolcompared to 47.4%±40.5% in the placebo group (p<0.04). In absoluteterms, the mean dose of prednisone was reduced from 11.9 mg to 3.9 mg inthe mepolizumab group and from 10.7 to 6.4 mg in the placebo group(median reduction in the two groups, from 10 to 5 mg) (P=0.11).

Pre-Specified Subgroup Analyses

Data for 8 of the 10 patients in the placebo group who had anexacerbation accompanied by sputum eosinophilia and were censored atthat time, while none of the patients who received mepolizumab had anexacerbation associated with sputum eosinophilia (P=0.02). There werethree exacerbations in the placebo group associated with sputumneutrophilia. In the mepolizumab group, there were five episodes ofincreased numbers of sputum neutrophils (in four patients) duringroutine visits, but the episodes were not associated with a change inthe measures that defined an exacerbation and thus were not treated.

In the mepolizumab group, there was a mean (±SD) reduction in use ofprednisone by 94.3%±12.9% of the maximum possible reduction per protocolcompared with 47.5%±42.2% in the placebo group (p=0.01).

Pre-Specified Secondary Outcomes

A single infusion of mepolizumab was associated with a reduction in thenumber of eosinophils to within normal limits in sputum (P=0.005) andblood (P=0.004). The levels remained within normal limits afterreductions in the dose of prednisone for up to 8 weeks after the lastinfusion of mepolizumab (P=0.01). In contrast, a reduction in the doseof prednisone in the placebo group was associated with a significantincrease in the number of eosinophils in sputum and blood (FIG. 3 andTable 3). There was no significant effect of mepolizumab on cell typesother than eosinophils in sputum or blood, except for a significantreduction of lymphocytes in sputum 4 weeks after the fifth infusion(P=0.001). Mepolizumab treatment was associated with a modestimprovement in FEV₁ (mean 300 ml), a nonsignificant improvement inasthma symptoms, and a significant improvement in scores on the JuniperAsthma Control Questionnaire (P=0.01) (Table 3 and FIG. 3).

Secondary Outcomes

A single infusion of mepolizumab reduced sputum and blood eosinophils towithin normal limits, where they remained after reductions of prednisonedose (p<0.05) and for up to 8 weeks after the last infusion ofmepolizumab. In contrast, sputum and blood eosinophils increasedsignificantly with prednisone reduction in the placebo arm (Table 4).Mepolizumab treatment was associated with the improvement in FEV₁,asthma symptoms and asthma control questionnaire score as shown in Table3.

A summary of variables before and after treatment for patients treatedwith mepolizumab are presented in Table 3. A summary of variables beforeand after treatment for patients treated with placebo are presented inTable 4.

TABLE 2A Variables before and after treatment with mepolizumab. Visit 4Visit 12 Visit 14 Visit 1 4 weeks post 4 weeks post 8 weeks postVariables Baseline First dose Last dose Last dose Number of patients 9 97 7 Sputum eosinophils (%) Median 16.6 0.0† 1.3† 0.3† Range 1.6-54.30-4.0 0.0-11.3 0.0-4.6 Blood eosinophils ± per mm³ 664.4 ± 492.5  49.5 ±37.46† 64.5 ± 37.94†  76.3 ± 39.36† FEV₁ after bronchodilation Value ±Liters 2.0 ± 0.88 2.1 ± 0.99  2.4 ± 1.06‡  2.3 ± 0.87 % of predictedvalue 66.6 ± 18.25 69.7 ± 17.7  71.9 ± 17.3‡  70.3 ± 13.2 Juniper AsthmaControl Questionnaire^(a) 1.9 ± 0.78 1.3 ± 0.91† 1.2 ± 0.81†  1.3 ±0.91† Cough Score^(b) 6.0 ± 0.82 5.2 ± 0.80† 5.3 ± 0.96†  5.5 ± 1.00Symptoms Score^(c) 29.4 ± 2.9  28.7 ± 4.9   31.6 ± 2.30  30.1 ± 4.02Plus-minus values are means ± SD. FEV₁ denotes forced expiry volume in 1second. †P < 0.05 for the comparison with baseline value. ‡P < 0.05 forthe comparison with the corresponding change from baseline in theplacebo group. ^(a)The Juniper Asthma Control Questionnaire score rangesfrom 0 to 6, with higher scores indicating worse control. ^(b)The coughscore, which was measured only in patients without current asthma atscreening, ranges from 1 to 7, with lower scores indicating a greaterseverity of symptoms. ^(c)The symptoms score ranges from 7 to 35 withlower scores indicating greater severity of symptoms. This scoreconsists of a composite rating of shortness of breath, chest tightness,wheezing, cough, and sputum production each graded on a 7-point Likertscale.

TABLE 2B Variables before and after treatment with placebo Visit 4 Visit12 Visit 14 Visit 1 4 weeks post 4 weeks post 8 weeks post 4 weeks postVariables Baseline First dose Last dose Last dose ExacerbationExacerbation Number of patients 11   10   2   2   9   9   Sputumeosinophils (%) Median 4.0 3.0 3.2 5.0 25.3 4.0 Range 0-35.3 0.0-16.31.3-5.0 1.0-9.0 5.0-63.7 1.3-52.5 Blood eosinophils ± per mm³ 352.1 ±253.74 295.8 ± 207.39 657.0 ± 413.23 1224.0 ± 1383.03 655.5 ± 254.77622.4 ± 498.4 FEV₁ after bronchodilation Value ± Liters 2.2 ± 0.92 2.3 ±0.94 2.3 ± 0.44 2.3 ± 0.39 2.0 ± 0.97 2.2 ± 0.8 % of predicted value74.3 ± 17.8  75.6 ± 17.0  78.4 ± 20.9  78.1 ± 19.2  60.9 ± 20.7  74.4 ±14.4 Juniper Asthma Control 1.8 ± 0.92 1.6 ± 0.88 1.2 ± 0.52 1.2 ± 0.282.0 ± 1.04 1.6 ± 1.4 Questionnaire^(a) Cough Score^(b) 6.3 ± 0.96  5.2 ±1.2 NA NA 5.8 ± 1.1  6.2 ± 1.0 Symptoms Score^(c) 29.8 ± 5.14  30.8 ±2.9 33.2 ± 1.56  32.5 ± 3.54  27.2 ± 4.18  29.4 ± 7.3  Plus-minus valuesare means ± SD. FEV₁ denotes forced expiry volume in 1 second and NA notapplicable. ^(a)The Juniper Asthma Control Questionnaire score rangesfrom 0 to 6, with higher scores indicating worse control. ^(b)The coughscore, which was measured only in patients without current asthma atscreening, ranges from 1 to 7, with lower scores indicating a greaterseverity of symptoms. ^(c)The symptoms score ranges from 7 to 35 withlower scores indicating greater severity of symptoms. This scoreconsists of a composite rating of shortness of breath, chest tightness,wheezing, cough, and sputum production each graded on a 7-point Likertscale.Safety

One patient in the mepolizumab group had progressive shortness of breathafter receiving three infusions of the drug and was removed from thestudy. Investigators, who were unaware of study-group assignments,determined that this patient had preexisting coronary artery disease;the breathlessness was attributable to heart failure due to ischemiccardiomyopathy. The patient did not undergo endocardial biopsy orcardiac magnetic resonance imaging to rule out eosinophiliccardiomyopathy. One patient in the placebo group died suddenly at home,6 months after the completing the full study. On autopsy, the cause ofdeath was identified as sudden cardiac arrest possibly due to aventricular tachyarrhythmia and was not ascribed to worsening asthma.One patient in the mepolizumab group reported having aches and tirednesswhen the prednisone dose was reduced to 2.5 mg. One patient in theplacebo group had hypoadrenalism during the prednisone reduction from12.5 mg to 5 mg per day (as demonstrated by a blunted cortisol responseto a short corticotrophin stimulation test). There were no other seriousadverse events. There were no significant abnormalities in bloodchemical values attributable to mepolizumab.

Discussion

These data show that in the rare patient with asthma who continues tohave sputum eosinophilia even when treated with oral prednisone and highdose inhaled corticosteroids, that treatment with a humanized monoclonalantibody against IL-5 allows a reduction in prednisone dose without thedevelopment of asthma exacerbations. These results are contrary to thenegative results of earlier studies with a similar antibody (Leckie, etal. Lancet 2000; 356: 2144-8; Kips, et al. Am J Respir Crit. Care Med2003; 167: 1655-9; and Flood-Page, et al. Am J Respir Crit. Care Med2007; 176: 1062-71) in patients with more common forms of asthma and inconcordance with those in hypereosinophilia syndrome (HES) (Klion, etal. Blood 2004; 103: 2939-2941; Garrett, et al. J Allergy Clin Immunol2004; 113: 115-119; and Rothenberg, et al. N Engl J Med 2008; 358:1215-28), and in two case report abstracts of asthma with sputumeosinophilia (Korn, et al. Am J Respir Crit. Care Med 2007; 175: A486)and HES with asthma (Hargreave, et al. Clin Exp Allergy (abstract) 2004;34: 1807).

In patients in the present study, with adult onset asthma, sputumeosinophilia that persisted in the presence of oral and inhaledcorticosteroid treatment was reversed by the anti-IL-5 treatment and thepatients improved clinically. In contrast, in the earlier studies,sputum eosinophils were either not measured, or there was little or nosputum eosinophilia at the onset of the study (Kips, et al. Am J RespirCrit. Care Med 2003; 167: 1655-9 and Flood-Page, et al. Am J RespirCrit. Care Med 2007; 176: 1062-71). None of the prior studies reportedthe effect of this treatment on the small subset of patients withbaseline airway eosinophilia. It is thus possible that the lack ofclinical benefit in previous trials was because the majority of patientsrandomized did not have the clinical phenotype we studied, persistentairway eosinophilia despite corticosteroid treatment.

This study has significant limitations. First, there was an imbalance inthe starting percentage of sputum eosinophils between the twotreatments, with the mepolizumab group having a higher sputum eosinophilcount. It is possible that the patients who respond to mepolizumab arethose with the highest numbers of eosinophils in sputum despitecorticosteroid treatment. Second, although the study demonstrated asignificant prednisone-sparing effect, there was no statisticallysignificant difference in the more clinically meaningful outcome of thefinal prednisone doses in the two treatment groups. Third, the studyrelied on past objective evidence of asthma as indicated by variableairflow limitation. Since most patients had frequent exacerbations inthe past and were on a maintenance dose of long-acting bronchodilator orhad moderate airflow obstruction at baseline, the study did not re-testfor albuterol reversibility or methacholine airway hyperresponsivenessin all patients at baseline. Fourth, the patients studied represent onlya small proportion of patients with asthma and persistent sputumeosinophilia and our results likely do not apply to most patients withasthma. Fifth, despite efforts, investigators may not have remainedcompletely blinded to treatment allocation because they were in partaware of sputum cell counts. Sixth the study is quite small and cannotbe considered clinically directive.

In summary, intravenous mepolizumab reduces blood and sputum eosinophilsand is prednisone-sparing in patients with asthma who had sputumeosinophils despite oral prednisone and high dose inhaled steroidtreatment. This small pilot study is potentially clinically directiveand highlights the importance of selecting subjects with airwayeosinophilia to study an anti-eosinophil drug in asthma.

The invention claimed is:
 1. A method for treating steroid dependenteosinophilic bronchitis in a human in need thereof and reducing a dailydose of steroid received by the human comprising the steps of: a)identifying a human receiving an initial daily dose of at least onesteroid selected from the group consisting of prednisone andprednisolone, for steroid dependent eosinophilic bronchitis; b)administering to the human a composition comprising at least oneanti-IL-5 antibody; c) reducing the initial daily dose of the at leastone steroid received by at least 90%; and d) administering the reduceddaily dose of steroid to the human; whereby the steroid dependenteosinophilic bronchitis is treated and the daily dose of steroidreceived by the human is reduced.
 2. The method of claim 1, wherein saidat least one anti-IL-5 antibody binds to human IL-5.
 3. The method ofclaim 2, wherein said at least one anti-IL-5 antibody is neutralizing.4. The method of claim 1, wherein said at least one anti-IL-5 antibodyis humanized.
 5. The method of claim 1, wherein said at least oneanti-IL-5 antibody comprises a heavy chain comprising SEQ ID NO:
 19. 6.The method of claim 1, wherein said at least one anti-IL-5 antibodycomprises a light chain comprising SEQ ID NO:
 21. 7. The method of claim1, wherein said human is suffering from at least one additional disorderassociated with excess eosinophil production selected from the groupconsisting of atopic asthma, atopic dermatitis, allergic rhinitis,non-allergic rhinitis, asthma, severe asthma, chronic eosinophilicpneumonia, allergic bronchopulmonary aspergillosis, coeliac disease,Churg-Strauss syndrome, eosinophilic myalgia syndrome, hypereosinophilicsyndrome, oedematous reactions including episodic angiodema, helminthinfections, eosinophilia associated with a parasitic infection,eosinophilia associated with the treatment of parasitic infection,onchocercal dermatitis, eosinophilic oesophagitis, eosinophilicgastritis, eosinophilic gastroenteritis, eosinophilic enteritis,eosinophilic colitis, nasal micropolyposis, nasal polyposis, aspirinintolerance asthma, obstructive sleep apnoea, chronic asthma, Crohn'sdisease, scleroderma and endomyocardial fibrosis.
 8. The method of claim1, wherein said composition comprising at least one anti-IL-5 antibodyis administered intravenously.
 9. The method of claim 8, wherein saidcomposition comprising at least one anti-IL-5 antibody is administeredat a dose of 750 mg.
 10. The method of claim 8, wherein said compositionis administered intravenously over 30 minutes.
 11. The method of claim1, wherein the human suffering from steroid dependent eosinophilicbronchitis experiences a reduction in exacerbations of eosinophilicbronchitis after receiving at least one dose of said compositioncomprising at least one anti-IL-5 antibody.
 12. The method of claim 1,wherein the eosinophil level in said human is reduced to within normallimits after at least one dose of said composition comprising at leastone anti-IL-5 antibody.
 13. The method of claim 12, wherein saideosinophil level remains within normal limits for at least 8 weeks afterthe last dose of said composition comprising at least one anti-IL-5antibody.
 14. The method of claim 1, wherein said composition comprisingat least one anti-IL-5 antibody comprises a first anti-IL-5 antibody anda second anti-IL-5 antibody.
 15. The method of claim 1, wherein saidcomposition comprising at least one anti-IL-5 antibody isco-administered with the at least one steroid.
 16. The method of claim12, wherein said eosinophil level is reduced in said human in at leastone selected from the group consisting of blood and sputum.
 17. Themethod of claim 1, wherein the patient also suffers from asthma.
 18. Amethod for treating steroid dependent eosinophilic bronchitis in a humanin need thereof and reducing a daily dose of steroid received by thehuman comprising the steps of: a) identifying a human receiving a dailydose of at least one steroid selected from the group consisting ofprednisone and prednisolone, for steroid dependent eosinophilicbronchitis; b) administering to the human a 25 mg dose of the at leastone steroid and administering to the human a composition comprising atleast one anti-IL-5 antibody; c) administering to the human a 25 mgdaily dose of the at least one steroid for about four weeks; d)administering to the human a 20 mg dose of the at least one steroid andadministering the composition; e) administering to the human a 20 mgdaily dose of the at least one steroid for about four weeks; f)administering to the human a 15 mg dose of the at least one steroid andadministering to the human the composition; g) administering to thehuman a 15 mg daily dose of the at least one steroid for about fourweeks; h) administering to the human a 10 mg dose of the at least onesteroid and administering to the human the composition; i) administeringto the human a 10 mg daily dose of the at least one steroid for aboutfour weeks; j) administering to the human a 7.5 mg dose of the at leastone steroid and administering to the human the composition; and k)administering to the human a 7.5 mg daily dose of the at least onesteroid; whereby the steroid dependent eosinophilic bronchitis istreated and the daily dose of steroid received by the human is reduced.19. The method of claim 18, wherein said at least one anti-IL-5 antibodybinds to human IL-5.
 20. The method of claim 19, wherein said at leastone anti-IL-5 antibody is neutralizing.
 21. The method of claim 18,wherein said at least one anti-IL-5 antibody is humanized.
 22. Themethod of claim 18, wherein said at least one anti-IL-5 antibodycomprises a heavy chain comprising SEQ ID NO:
 19. 23. The method ofclaim 18, wherein said at least one anti-IL-5 antibody comprises a lightchain comprising SEQ ID NO:
 21. 24. The method of claim 18, wherein saidhuman is suffering from at least one additional disorder associated withexcess eosinophil production selected from the group consisting ofatopic asthma, atopic dermatitis, allergic rhinitis, non-allergicrhinitis, asthma, severe asthma, chronic eosinophilic pneumonia,allergic bronchopulmonary aspergillosis, coeliac disease, Churg-Strausssyndrome, eosinophilic myalgia syndrome, hypereosinophilic syndrome,oedematous reactions including episodic angiodema, helminth infections,eosinophilia associated with a parasitic infection, eosinophiliaassociated with the treatment of parasitic infection, onchocercaldermatitis, eosinophilic oesophagitis, eosinophilic gastritis,eosinophilic gastroenteritis, eosinophilic enteritis, eosinophiliccolitis, nasal micropolyposis, nasal polyposis, aspirin intoleranceasthma, obstructive sleep apnoea, chronic asthma, Crohn's disease,scleroderma and endomyocardial fibrosis.
 25. The method of claim 18,wherein said composition comprising at least one anti-IL-5 antibody isadministered intravenously.
 26. The method of claim 25, wherein saidcomposition comprising at least one anti-IL-5 antibody is administeredat a dose of 750 mg.
 27. The method of claim 25, wherein saidcomposition is administered intravenously over 30 minutes.
 28. Themethod of claim 18, wherein the human suffering from steroid dependenteosinophilic bronchitis experiences a reduction in exacerbations ofeosinophilic bronchitis after receiving at least one dose of saidcomposition comprising at least one anti-IL-5 antibody.
 29. The methodof claim 18, wherein the eosinophil level in said human is reduced towithin normal limits after at least one dose of said compositioncomprising at least one anti-IL-5 antibody.
 30. The method of claim 29,wherein said eosinophil level remains within normal limits for at least8 weeks after the last dose of said composition comprising at least oneanti-IL-5 antibody.
 31. The method of claim 18, wherein said compositioncomprising at least one anti-IL-5 antibody comprises a first anti-IL-5antibody and a second anti-IL-5 antibody.
 32. The method of claim 29,wherein said eosinophil level is reduced in said human in at least oneselected from the group consisting of blood and sputum.
 33. The methodof claim 18, wherein the patient also suffers from asthma.
 34. A methodfor treating steroid dependent eosinophilic bronchitis in a human inneed thereof and reducing a daily dose of steroid received by the humancomprising the steps of: a) identifying a human receiving a daily doseof at least one steroid selected from the group consisting of prednisoneand prednisolone, for steroid dependent eosinophilic bronchitis; b)administering to the human a 20 mg dose of the at least one steroid andadministering to the human a composition comprising at least oneanti-IL-5 antibody; c) administering to the human a 20 mg daily dose ofthe at least one steroid for about four weeks; d) administering to thehuman a 15 mg dose of the at least one steroid and administering to thehuman the composition; e) administering to the human a 15 mg daily doseof the at least one steroid for about four weeks; f) administering tothe human a 10 mg dose of the at least one steroid and administering tothe human the composition; g) administering to the human a 10 mg dailydose of the at least one steroid for about four weeks; h) administeringto the human a 7.5 mg dose of the at least one steroid and administeringthe composition; i) administering to the human a 7.5 mg daily dose ofthe at least one steroid for about four weeks; j) administering to thehuman a 5 mg dose of the at least one steroid and administering to thehuman the composition; and k) administering to the human a 5 mg dailydose of the at least one steroid; whereby the steroid dependenteosinophilic bronchitis is treated and the daily dose of steroidreceived by the human is reduced.
 35. The method of claim 34, whereinsaid at least one anti-IL-5 antibody binds to human IL-5.
 36. The methodof claim 35, wherein said at least one anti-IL-5 antibody isneutralizing.
 37. The method of claim 34, wherein said at least oneanti-IL-5 antibody is humanized.
 38. The method of claim 34, whereinsaid at least one anti-IL-5 antibody comprises a heavy chain comprisingSEQ ID NO:
 19. 39. The method of claim 34, wherein said at least oneanti-IL-5 antibody comprises a light chain comprising SEQ ID NO:
 21. 40.The method of claim 34, wherein said human is suffering from at leastone additional disorder associated with excess eosinophil productionselected from the group consisting of atopic asthma, atopic dermatitis,allergic rhinitis, non-allergic rhinitis, asthma, severe asthma, chroniceosinophilic pneumonia, allergic bronchopulmonary aspergillosis, coeliacdisease, Churg-Strauss syndrome, eosinophilic myalgia syndrome,hypereosinophilic syndrome, oedematous reactions including episodicangiodema, helminth infections, eosinophilia associated with a parasiticinfection, eosinophilia associated with the treatment of parasiticinfection, onchocercal dermatitis, eosinophilic oesophagitis,eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilicenteritis, eosinophilic colitis, nasal micropolyposis, nasal polyposis,aspirin intolerance asthma, obstructive sleep apnoea, chronic asthma,Crohn's disease, scleroderma and endomyocardial fibrosis.
 41. The methodof claim 34, wherein said composition comprising at least one anti-IL-5antibody is administered intravenously.
 42. The method of claim 41,wherein said composition comprising at least one anti-IL-5 antibody isadministered at a dose of 750 mg.
 43. The method of claim 41, whereinsaid composition is administered intravenously over 30 minutes.
 44. Themethod of claim 34, wherein the human suffering from steroid dependenteosinophilic bronchitis experiences a reduction in exacerbations ofeosinophilic bronchitis after receiving at least one dose of saidcomposition comprising at least one anti-IL-5 antibody.
 45. The methodof claim 34, wherein the eosinophil level in said human is reduced towithin normal limits after at least one dose of said compositioncomprising at least one anti-IL-5 antibody.
 46. The method of claim 45,wherein said eosinophil level remains within normal limits for at least8 weeks after the last dose of said composition comprising at least oneanti-IL-5 antibody.
 47. The method of claim 34, wherein said compositioncomprising at least one anti-IL-5 antibody comprises a first anti-IL-5antibody and a second anti-IL-5 antibody.
 48. The method of claim 45,wherein said eosinophil level is reduced in said human in at least oneselected from the group consisting of blood and sputum.
 49. The methodof claim 34, wherein the patient also suffers from asthma.
 50. A methodfor treating steroid dependent eosinophilic bronchitis in a human inneed thereof and reducing a daily dose of steroid received by the humancomprising the steps of: a) identifying a human receiving a daily doseof at least one steroid selected from the group consisting of prednisoneand prednisolone, for steroid dependent eosinophilic bronchitis; b)administering to the human a 15 mg dose of the at least one steroid andadministering to the human a composition comprising at least oneanti-IL-5 antibody; c) administering to the human a 15 mg daily dose ofthe at least one steroid for about four weeks; d) administering to thehuman a 10 mg dose of the at least one steroid and administering to thehuman the composition; e) administering to the human a 10 mg daily doseof the at least one steroid for about four weeks; f) administering tothe human a 7.5 mg dose of the at least one steroid and administering tothe human the composition; g) administering to the human a 7.5 mg dailydose of the at least one steroid for about four weeks; h) administeringto the human a 5 mg dose of the at least one steroid and administeringto the human the composition; and i) administering to the human a 5 mgdaily dose of the at least one steroid for about four weeks; whereby thesteroid dependent eosinophilic bronchitis is treated and the daily doseof steroid received by the human is reduced.
 51. The method of claim 50,wherein said at least one anti-IL-5 antibody binds to human IL-5. 52.The method of claim 51, wherein said at least one anti-IL-5 antibody isneutralizing.
 53. The method of claim 50, wherein said at least oneanti-IL-5 antibody is humanized.
 54. The method of claim 50, whereinsaid at least one anti-IL-5 antibody comprises a heavy chain comprisingSEQ ID NO:
 19. 55. The method of claim 50, wherein said at least oneanti-IL-5 antibody comprises a light chain comprising SEQ ID NO:
 21. 56.The method of claim 50, wherein said human is suffering from at leastone additional disorder associated with excess eosinophil productionselected from the group consisting of atopic asthma, atopic dermatitis,allergic rhinitis, non-allergic rhinitis, asthma, severe asthma, chroniceosinophilic pneumonia, allergic bronchopulmonary aspergillosis, coeliacdisease, Churg-Strauss syndrome, eosinophilic myalgia syndrome,hypereosinophilic syndrome, oedematous reactions including episodicangiodema, helminth infections, eosinophilia associated with a parasiticinfection, eosinophilia associated with the treatment of parasiticinfection, onchocercal dermatitis, eosinophilic oesophagitis,eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilicenteritis, eosinophilic colitis, nasal micropolyposis, nasal polyposis,aspirin intolerance asthma, obstructive sleep apnoea, chronic asthma,Crohn's disease, scleroderma and endomyocardial fibrosis.
 57. The methodof claim 50, wherein said composition comprising at least one anti-IL-5antibody is administered intravenously.
 58. The method of claim 57,wherein said composition comprising at least one anti-IL-5 antibody isadministered at a dose of 750 mg.
 59. The method of claim 57, whereinsaid composition is administered intravenously over 30 minutes.
 60. Themethod of claim 50, wherein the human suffering from steroid dependenteosinophilic bronchitis experiences a reduction in exacerbations ofeosinophilic bronchitis after receiving at least one dose of saidcomposition comprising at least one anti-IL-5 antibody.
 61. The methodof claim 50, wherein the eosinophil level in said human is reduced towithin normal limits after at least one dose of said compositioncomprising at least one anti-IL-5 antibody.
 62. The method of claim 61,wherein said eosinophil level remains within normal limits for at least8 weeks after the last dose of said composition comprising at least oneanti-IL-5 antibody.
 63. The method of claim 50, wherein said compositioncomprising at least one anti-IL-5 antibody comprises a first anti-IL-5antibody and a second anti-IL-5 antibody.
 64. The method of claim 61,wherein said eosinophil level is reduced in said human in at least oneselected from the group consisting of blood and sputum.
 65. The methodof claim 50, wherein the patient also suffers from asthma.
 66. A methodfor treating steroid dependent eosinophilic bronchitis in a human inneed thereof and reducing a daily dose of steroid received by the humancomprising the steps of: a) identifying a human receiving a daily doseof at least one steroid selected from the group consisting of prednisoneand prednisolone, for steroid dependent eosinophilic bronchitis; b)administering to the human a 10 mg dose of the at least one steroid andadministering to the human a composition comprising at least oneanti-IL-5 antibody; c) administering to the human a 10 mg daily dose ofthe at least one steroid for about four weeks; d) administering to thehuman a 7.5 mg dose of the at least one steroid and administering to thehuman the composition; e) administering to the human a 7.5 mg daily doseof the at least one steroid for about four weeks; f) administering tothe human a 5 mg dose of the at least one steroid and administering tothe human the composition; g) administering to the human a 5 mg dailydose of the at least one steroid for about four weeks; h) administeringto the human a 2.5 mg dose of the at least one steroid and administeringto the human the composition; and i) administering to the human a 2.5 mgdaily dose of the at least one steroid for about four weeks; whereby thesteroid dependent eosinophilic bronchitis is treated and the daily doseof steroid received by the human is reduced.
 67. The method of claim 66,wherein said at least one anti-IL-5 antibody binds to human IL-5. 68.The method of claim 67, wherein said at least one anti-IL-5 antibody isneutralizing.
 69. The method of claim 66, wherein said at least oneanti-IL-5 antibody is humanized.
 70. The method of claim 66, whereinsaid at least one anti-IL-5 antibody comprises a heavy chain comprisingSEQ ID NO:
 19. 71. The method of claim 66, wherein said at least oneanti-IL-5 antibody comprises a light chain comprising SEQ ID NO:
 21. 72.The method of claim 66, wherein said human is suffering from at leastone additional disorder associated with excess eosinophil productionselected from the group consisting of atopic asthma, atopic dermatitis,allergic rhinitis, non-allergic rhinitis, asthma, severe asthma, chroniceosinophilic pneumonia, allergic bronchopulmonary aspergillosis, coeliacdisease, Churg-Strauss syndrome, eosinophilic myalgia syndrome,hypereosinophilic syndrome, oedematous reactions including episodicangiodema, helminth infections, eosinophilia associated with a parasiticinfection, eosinophilia associated with the treatment of parasiticinfection, onchocercal dermatitis, eosinophilic oesophagitis,eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilicenteritis, eosinophilic colitis, nasal micropolyposis, nasal polyposis,aspirin intolerance asthma, obstructive sleep apnoea, chronic asthma,Crohn's disease, scleroderma and endomyocardial fibrosis.
 73. The methodof claim 66, wherein said composition comprising at least one anti-IL-5antibody is administered intravenously.
 74. The method of claim 73,wherein said composition comprising at least one anti-IL-5 antibody isadministered at a dose of 750 mg.
 75. The method of claim 73, whereinsaid composition is administered intravenously over 30 minutes.
 76. Themethod of claim 66, wherein the human suffering from steroid dependenteosinophilic bronchitis experiences a reduction in exacerbations ofeosinophilic bronchitis after receiving at least one dose of saidcomposition comprising at least one anti-IL-5 antibody.
 77. The methodof claim 66, wherein the eosinophil level in said human is reduced towithin normal limits after at least one dose of said compositioncomprising at least one anti-IL-5 antibody.
 78. The method of claim 77,wherein said eosinophil level remains within normal limits for at least8 weeks after the last dose of said composition comprising at least oneanti-IL-5 antibody.
 79. The method of claim 66, wherein said compositioncomprising at least one anti-IL-5 antibody comprises a first anti-IL-5antibody and a second anti-IL-5 antibody.
 80. The method of claim 77,wherein said eosinophil level is reduced in said human in at least oneselected from the group consisting of blood and sputum.
 81. The methodof claim 66, wherein the patient also suffers from asthma.
 82. A methodfor treating steroid dependent eosinophilic bronchitis in a human inneed thereof and reducing a daily dose of steroid received by the humancomprising the steps of: a) identifying a human receiving a daily doseof at least one steroid selected from the group consisting of prednisoneand prednisolone, for steroid dependent eosinophilic bronchitis; b)administering to the human a 10 mg dose of the at least one steroid andadministering to the human a composition comprising at least oneanti-IL-5 antibody; c) administering to the human a 10 mg daily dose ofthe at least one steroid for about four weeks; d) administering to thehuman a 7.5 mg dose of the at least one steroid and administering to thehuman the composition; e) administering to the human a 7.5 mg daily doseof the at least one steroid for about four weeks; f) administering tothe human a 5 mg dose of the at least one steroid and administering tothe human the composition; and g) administering to the human a 5 mgdaily dose of the at least one steroid for about four weeks; whereby thesteroid dependent eosinophilic bronchitis is treated and the daily doseof steroid received by the human is reduced.
 83. The method of claim 82,wherein said at least one anti-IL-5 antibody binds to human IL-5. 84.The method of claim 83, wherein said at least one anti-IL-5 antibody isneutralizing.
 85. The method of claim 82, wherein said at least oneanti-IL-5 antibody is humanized.
 86. The method of claim 82, whereinsaid at least one anti-IL-5 antibody comprises a heavy chain comprisingSEQ ID NO:
 19. 87. The method of claim 82, wherein said at least oneanti-IL-5 antibody comprises a light chain comprising SEQ ID NO:
 21. 88.The method of claim 82, wherein said human is suffering from at leastone additional disorder associated with excess eosinophil productionselected from the group consisting of atopic asthma, atopic dermatitis,allergic rhinitis, non-allergic rhinitis, asthma, severe asthma, chroniceosinophilic pneumonia, allergic bronchopulmonary aspergillosis, coeliacdisease, Churg-Strauss syndrome, eosinophilic myalgia syndrome,hypereosinophilic syndrome, oedematous reactions including episodicangiodema, helminth infections, eosinophilia associated with a parasiticinfection, eosinophilia associated with the treatment of parasiticinfection, onchocercal dermatitis, eosinophilic oesophagitis,eosinophilic gastritis, eosinophilic gastroenteritis, eosinophilicenteritis, eosinophilic colitis, nasal micropolyposis, nasal polyposis,aspirin intolerance asthma, obstructive sleep apnoea, chronic asthma,Crohn's disease, scleroderma and endomyocardial fibrosis.
 89. The methodof claim 82, wherein said composition comprising at least one anti-IL-5antibody is administered intravenously.
 90. The method of claim 89,wherein said composition comprising at least one anti-IL-5 antibody isadministered at a dose of 750 mg.
 91. The method of claim 89, whereinsaid composition is administered intravenously over 30 minutes.
 92. Themethod of claim 82, wherein the human suffering from steroid dependenteosinophilic bronchitis experiences a reduction in exacerbations ofeosinophilic bronchitis after receiving at least one dose of saidcomposition comprising at least one anti-IL-5 antibody.
 93. The methodof claim 82, wherein the eosinophil level in said human is reduced towithin normal limits after at least one dose of said compositioncomprising at least one anti-IL-5 antibody.
 94. The method of claim 93,wherein said eosinophil level remains within normal limits for at least8 weeks after the last dose of said composition comprising at least oneanti-IL-5 antibody.
 95. The method of claim 82, wherein said compositioncomprising at least one anti-IL-5 antibody comprises a first anti-IL-5antibody and a second anti-IL-5 antibody.
 96. The method of claim 93,wherein said eosinophil level is reduced in said human in at least oneselected from the group consisting of blood and sputum.
 97. The methodof claim 82, wherein the patient also suffers from asthma.
 98. A methodfor treating steroid dependent eosinophilic bronchitis in a human inneed thereof and eliminating a daily dose of steroid received by thehuman comprising the steps of: a) identifying a human receiving a dailydose of at least one steroid selected from the group consisting ofprednisone and prednisolone, for steroid dependent eosinophilicbronchitis; b) administering to the human a 5 mg dose of the at leastone steroid and administering to the human a composition comprising atleast one anti-IL-5 antibody; c) administering to the human a 5 mg dailydose of the at least one steroid for about four weeks; d) administeringto the human a 2.5 mg dose of the at least one steroid and administeringto the human the composition; e) administering to the human a 2.5 mgdaily dose of the at least one steroid for about four weeks; and f)administering to the human the composition and discontinuing dailyadministration of the at least one steroid; whereby the steroiddependent eosinophilic bronchitis is treated and the daily dose ofsteroid received by the human is eliminated.
 99. The method of claim 98,wherein said at least one anti-IL-5 antibody binds to human IL-5. 100.The method of claim 98, wherein said at least one anti-IL-5 antibody isneutralizing.
 101. The method of claim 98, wherein said at least oneanti-IL-5 antibody is humanized.
 102. The method of claim 98, whereinsaid at least one anti-IL-5 antibody comprises a heavy chain comprisingSEQ ID NO:
 19. 103. The method of claim 98, wherein said at least oneanti-IL-5 antibody comprises a light chain comprising SEQ ID NO: 21.104. The method of claim 98, wherein said human is suffering from atleast one additional disorder associated with excess eosinophilproduction selected from the group consisting of atopic asthma, atopicdermatitis, allergic rhinitis, non-allergic rhinitis, asthma, severeasthma, chronic eosinophilic pneumonia, allergic bronchopulmonaryaspergillosis, coeliac disease, Churg-Strauss syndrome, eosinophilicmyalgia syndrome, hypereosinophilic syndrome, oedematous reactionsincluding episodic angiodema, helminth infections, eosinophiliaassociated with a parasitic infection, eosinophilia associated with thetreatment of parasitic infection, onchocercal dermatitis, eosinophilicoesophagitis, eosinophilic gastritis, eosinophilic gastroenteritis,eosinophilic enteritis, eosinophilic colitis, nasal micropolyposis,nasal polyposis, aspirin intolerance asthma, obstructive sleep apnoea,chronic asthma, Crohn's disease, scleroderma and endomyocardialfibrosis.
 105. The method of claim 98, wherein said compositioncomprising at least one anti-IL-5 antibody is administeredintravenously.
 106. The method of claim 105, wherein said compositioncomprising at least one anti-IL-5 antibody is administered at a dose of750 mg.
 107. The method of claim 105, wherein said composition isadministered intravenously over 30 minutes.
 108. The method of claim 98,wherein the human suffering from steroid dependent eosinophilicbronchitis experiences a reduction in exacerbations of eosinophilicbronchitis after receiving at least one dose of said compositioncomprising at least one anti-IL-5 antibody.
 109. The method of claim 98,wherein the eosinophil level in said human is reduced to within normallimits after at least one dose of said composition comprising at leastone anti-IL-5 antibody.
 110. The method of claim 109, wherein saideosinophil level remains within normal limits for at least 8 weeks afterthe last dose of said composition comprising at least one anti-IL-5antibody.
 111. The method of claim 98, wherein said compositioncomprising at least one anti-IL-5 antibody comprises a first anti-IL-5antibody and a second anti-IL-5 antibody.
 112. The method of claim 109,wherein said eosinophil level is reduced in said human in at least oneselected from the group consisting of blood and sputum.
 113. The methodof claim 98, wherein the patient also suffers from asthma.